This invention relates to the administration of a therapeutic gas such as nitric oxide (NO) to patients for therapeutic effect. In particular, it relates to a system wherein a controlled, predetermined dose of NO is provided to the patient with each inhalation by the patient.
The function of the administration of NO has been fairly widely published and typical articles appeared in The Lancet, Vol. 340, October 1992 at pages 818-820 entitled "Inhaled Nitric Oxide in Persistent Pulmonary Hypertension of the Newborn" and "Low-dose Inhalation Nitric Oxide in Persistent Pulmonary Hypertension of the Newborn" and in Anesthesiology, Vol. 78, pgs. 413-416 (1993), entitled "Inhaled NO-the past, the present and the future".
The actual administration of NO is generally carried out by its introduction into the patient as a gas and commercially available supplies are provided in cylinders under pressure and may be at pressures of about 2000 psi and consist of a predetermined mixture of NO in a carrier gas such as nitrogen. A pressure regulator is therefore used to reduce the pressure of the supply cylinder to working levels for introduction to a patient.
The concentration administered to a patient will vary according to the patient and the need for the therapy but will generally include concentrations at or lower than 100 ppm. There is, of course, a need for that concentration to be precisely metered to the patient since an excess of NO can be harmful to the patient.
One current known method and apparatus for the administration of NO to patients is described in U.S. Pat. No. 5,558,083 where a system is provided that can be added to any ventilator and which will meter in the desired concentration of NO into the gas supplied from that ventilator.
Various other delivery devices have also been used that respond to the patient attempting to inhale to deliver a pulsed dose of NO to the patient and such pulsing devices have also been shown to have therapeutic effect on the patient, for example, as described in Higenbottam PCT patent application WO 95/10315 and the publication of Channick et al "Pulsed delivery of inhaled nitric oxide to patients with primary pulmonary hypertension", Chest/109/June 1996. In such pulsatile dosing devices, a pulse of NO is administered to the patient as the patient inhales spontaneously.
The inhalation pulsing type devices are typically shown and described in Durkan, U.S. Pat. No. 4,462,398, however the Durkan device has certain limitations and was designed for the administration of oxygen and not NO. Again, further devices are known, based somewhat on the Durkan device, such as described in Perkins U.S. Pat. No. 5,005,570 and Dietz U.S. Pat. No. 5,038,771. Again, however, the devices were principally designed for use in the administration of oxygen. One of the properties of NO is that it has a toxic effect at high concentrations while having its beneficial therapeutic effect at low concentrations. Additional hazards also exist from hypoxia with over delivery of NO as the balance gas for NO is nitrogen, high pulmonary arterial pressures which result in low PaO.sub.2 from under delivery of NO, and the conversion of NO in the presence of oxygen to nitrogen dioxide, NO.sub.2, which is a more toxic compound. Nitric oxide systems, therefore, require additional safeguards and control than with devices designed for the delivery of oxygen.
Basically, of the types known, the Durkan and Perkins approach to administration is based on the time that a flow control valve is open and thus the time that the gas is administered to the patient. With such a system, however, the device does not provide a fixed volume of gas to the patient under all conditions as a variation in input pressure, ambient temperature or altitude will result in a higher or lower flow of gas through the valve. Accordingly, with a fixed time interval, the differing flow will result in differing volumes being delivered per breath to the patient.
As an example, with a timed interval device the cylinder of gas will generally be reduced in pressure as the administration of the gas is carried out. The regulator that reduces the cylinder pressure to a working pressure, generally puts out a decreased pressure as the cylinder pressure is lowered, that is, as a direct function. Since that pressure downstream of the regulator varies, so does the flow to the patient and the actual volume dose of NO to the patient is, therefore, not constant with a constant timed dosage, but varies as the cylinder pressure varies.
The Dietz patent takes a differing approach, and which varies the time the valve is opened based on the size of the previous breath of the patient. Again, the volume delivered per breath is variable due to the input pressure and the altitude and is further dependent on the size of the breath itself, i.e. the larger the breath, the higher the dose provided to the patient. Such may not be required for NO therapy to the patient.
One further problem with the typical prior art devices is that there is no safety system to indicate when the timing valve has failed and thus, the patient may not be receiving the needed therapy from the device or may be receiving an excess of therapy.
As a further shortcoming of current known systems, the ambient temperature and pressure also have an effect on the dose of gas delivered during any timed pulse and thus can thereby affect the treatment of the individual that is receiving the NO therapy. The current devices do not take the ambient temperature or pressure into account in providing the pulse to the patient and therefore such devices can introduce inaccuracies in the particular dosage. With the use of NO, however, such inaccuracies can create a harmful situation to the patient.
Accordingly, with the use of such current devices for administering NO, the actual dose of the NO to the patient may vary and the exact dose is basically unknown, thus the control of the therapy is somewhat difficult and a need exists for more precise control of the dose of NO administered per breath and better alarms are required to indicate if there is unsafe over or under delivery of the NO therapy.